Andrew T. Raftery

Mesothelial Hyperplasia in Response to Peritoneal Dialysis Fluid A Morphometric Study in the Rat

Five rats were given twice daily intraperitoneal injections of hypertonic dialysis fluid for 6 weeks. The structure of the hepatic peritoneum of this group was compared with that of a control group by applying morphometric techniques to transmission electron micrographs. The experimental group showed marked mesothelial hyperplasia with doubling of the number of cells and a significant increase in the length of intercellular junction per unit area of peritoneum. Since cell volumes in the two groups were similar, the increase in cell density in the experimental animals was the result of the cells assuming a more cuboidal shape. Experimental animals also showed an increase in the number of microvilli, pinocytotic vesicles and rough endoplasmic reticulum per unit area of peritoneum. Chronic exposure to dialysis fluid has profound effects on the number, shape and composition of peritoneal mesothelial cells in the rat.

Reduction of ischemia-reperfusion injury in the rat kidney by FTY720, a synthetic derivative of sphingosine.

Background. The current shortage of organ donors has led many centers to use marginal and nonheart-beating donors (NHBDs). Recent research has implicated the infiltration of lymphocytes as an important mediator of ischemia–reperfusion injury (IRI). FTY720 is an immunosuppressant that promotes lymphocyte sequestration into lymph nodes. The purpose of this study was to examine the potential for FTY720 to abrogate IRI when subjected to increasing ischemic times. Methods. Male Sprague–Dawley rats underwent bilateral flank incision with removal of the right kidney and clamping of the left hilum. Groups were divided into ischemia times of 45, 55, and 65min; each group was further divided into a control group (IRI only), IRI+FTY720 (1 mg/kg/d), and IRI+cyclosporine (15 mg/kg/d), n=4 per group. Results. Thre days after 45 min of ischemia, serum creatinine in the ischemia only (477±37 &mgr;mol/L) and cyclosporine groups (698±32 &mgr;mol/L) was significantly increased compared with the FTY720-treated animals (194±66 &mgr;mol/L). The beneficial effect of FTY720 was also observed at 55 and 65 min; indeed, FTY720-treated animals demonstrated signs of recovery from 65 min of ischemia whereas control and cyclosporine-treated animals required sacrifice between days 3 and 5. Treatment with FTY720 reduced renal damage assessed histologically and also reduced apoptosis and increased cell proliferation. Conclusion. Treatment with FTY720 reduced IRI and prevented unrecoverable acute renal failure after significant ischemic injury. This study suggests that FTY720 may help improve the quality of grafts from NHBD and marginal donors by abrogating the IRI insult.

Historical perspectives in kidney transplantation: an updated review

The present state of success in kidney transplantation, including its benefits to patients with end-stage renal failure, was achieved through relentless research, both in experimental animal models and human volunteers. Kidney transplantation has evolved during the past century thanks to various milestones in surgical techniques, immunology, immunosuppressive drugs, expansion of donor sources, organ preservation, transplant against immunological barriers (ABO blood group-incompatible and positive crossmatch transplants), and research on induction of tolerance, xenotransplants, and stem cell technology. Despite significant improvements in graft and patient survival, several issues still must be addressed to reduce the growing number of patients with kidney failure waiting to receive organs. This article provides an up-to-date review of the milestones in the history of kidney transplantation and highlights strategies to resolve current problems faced by patients and the transplant community.

Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy

Background. Tissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft nephropathy (CAN). Materials and Methods. Left renal grafts from male Fisher and Lewis were transplanted into Lewis rats, generating allografts and isografts, respectively. Blood pressure, renal function, and proteinuria were monitored for up to 52 weeks. At termination, CAN was assessed in the renal tissue by light and electron microscopy, TG2 and ε(γ-glutamyl)-lysine by immunofluorescence, and the urinary ε(γ-glutamyl)-lysine by high performance liquid chromatography. Results. Compared to the isograft, the allografts were hypertensive, proteinuric, and uraemic and developed CAN. Extracellular TG2 (glomerulus: 64.55 ± 17.61 versus 2.11 ± 0.17, P < 0.001; interstitium: 13.72 ± 1.62 versus 3.19 ± 0.44, P < 0.001), ε(γ-glutamyl)-lysine (glomerulus: 21.74 ± 2.71 versus 1.98 ± 0.37, P < 0.01; interstitium: 37.96 ± 17.06 versus 0.42 ± 0.11, P < 0.05), TG2 enzyme activity (1.09 ± 0.13 versus 0.41 ± 0.03 nmol/h/mg protein, P < 0.05), TG2 mRNA (20-fold rise), and urinary ε(γ-glutamyl)-lysine (534.2 ± 198.4 nmol/24 h versus 57.2 ± 4.1 nmol/24 h, P < 0.05) levels were significantly elevated in the allografts and showed a positive linear correlation with tubulointerstitial fibrosis. Conclusion. CAN was associated with upregulation of renal TG2 pathway, which has a potential for pharmacological intervention. The elevated urinary ε(γ-glutamyl)-lysine, measured for the first time in RTx, is a potential biomarker of CAN.

THE ANATOMY AND PATHOLOGY OF THE LESSER SAC: IMPLICATIONS FOR PERITONEAL DIALYSIS

Pathological conditions involving the lesser sac of the peritoneal cavity in patients on peritoneal dialysis (PD) can pose significant diagnostic and therapeutic challenges. Lack of appreciation of these challenges may delay diagnosis and compromise outcome. A case series by Li and colleagues in this issue of Peritoneal Dialysis International highlights the diagnostic challenges presented by lesser sac infection in PD patients, and in this accompanying commentary we discuss the development and anatomy of the lesser sac, as well as the pathological conditions and investigations relevant to the management of patients on PD.

RENAL TRANSPLANTATION AFTER ENDOVASCULAR REPAIR OF ABDOMINAL AORTIC ANEURYSM: A SINGLE CENTRE EXPERIENCE: 1814

INTRODUCTION: Endovascular aneurysm repair (EVAR) is an effective modality of treatment for abdominal aortic aneurysm (AAA), particularly in patients with renal disease, because of advantages over the standard open procedure, including lower morbidity, shorter operative time and shorter hospital stay. There is paucity of data in the transplant literature on RT after EVAR. A Medline search showed two case reports on renal transplantation (RT) after EVAR, including the one from our institution. In this context, we present the outcomes of our two cases of successful RT following EVAR and discuss intraand post-operative issues pertinent to the subject. METHODS: Case 1: A 54-year-old male with end-stage renal failure secondary to membranous nephropathy, was treated successfully with EVAR for an 5.7 cm diameter AAA using an endovascular bifurcated stent graft, where the distal ends extended to the bifurcation of the common iliac arteries. He underwent a deceased donor RT 2 years after EVAR where renal vessels were anastomosed to the recipient external iliac (EI) vessels. A medial dissection occurred on the grossly atherosclerotic EI artery, which was repaired. The vascular anastomosis time was 60 minutes. Case 2: A 64 year-old male with ESRD of unknown cause underwent DD RT 18 months after undergoing EVAR. He has undergone coronary angioplasty and repair of right popliteal aneurysm 1 year ago. The donor renal artery anastomosed to the left EIA just distal to existing aneurysm of the CIA. The vascular anastomosis time was 37 minutes. RESULTS: Postoperatively, both transplants functioned immediately with progressive fall in the serum creatinine. Duplex and Mag3 scans showed well-perfused kidney with patent EI arteries. No dislodgement, migration, endoleak, dissection or thrombosis of the stent occurred. A follow-up computerised tomographic scan showed minor dissection of the EIA and normal renal allograft vessel in the first case 1 year after RT. CONCLUSIONS: Current evidences show favourable outcomes of EVAR in normal population, in patients with renal diseases and in renal transplant recipients. Although the long-term outcomes of RT after EVAR remain unknown, from the experience of our two successful RTs, we endorse RT in renal failure patients who have undergone EVAR in the past.